EXPRESSION OF FUNCTIONAL P-PLATELET- DERIVED GROWTH FACTOR RECEPTORS ON HEMATOPOIETIC CELL LINES Nathalie de Parseval, SergeFichelson , Patrick Mayeux, Sylvie Gisselbrecht , Brigitte Sola The P-type receptor of platelet-derived growth factor (PPDGFR) is a class III transmembrane receptor with tyrosine kinase activity. The PPDGFR gene is located on mouse chromosome 18 close to the c-fms gene which codes for the colony stimulating factor-l receptor (CSF-1R). We previously reported that in a high percentage of myeloblastic leukemias induced by the Friend helper murine leukemia virus (F-MuLV), proviruses were integrated in the first intron of the c-fins gene leading to an enhanced expression of c-fms mRNA. Since activation by proviral insertion can act at long distance, we studied PPDGF receptor gene expression in murine myeloblastic leukemias. This gene was found to be frequently expressed but the level of PPDGF receptor mRNA was weak and not related to proviral activation. High affinity binding sites were expressed on myeloblastic cells and ligand binding induced cell proliferation. To determine whether PPDGFR expression is a common feature in hematopoietic cells, we tested cell lines belonging to other hematopoietic lineages. We found that multipotent stem and mast cell lines also expressed the PPDGF receptor gerie. This suggests that PDGF, known as a mitogen for connective tissue cells, could also play a role in normal hematopoiesis. We previously reported that in myeloblastic leukemias induced by the Friend helper murine leukemia virus (F-MuLV), proviruses were fre- quently integrated in a region named Fim-2.1 This region encompassed the 5’-part of the c-fm protocogene which encodes the colony-stimulating factor-l receptor (CSF-lR).* The Fim-2 locus spans at least 15 kb in the c-frm 26 kb-long first intron and proviruses are always integrated upstream from the c-fms transcription initiation start used in monocytic cells. Proviral integration at this locus always led to high c-fm expression. 3 The CSF-1 receptor belongs to the type III tyrosine kinase receptor subfamily which is characterized by an extracellular ligand binding domain folded in five immunoglobulin-like domains From ICGM, INSERM U363 Paris V, HBpital Cochin, 27 Rue du Fbg St Jacques, 75014, Paris, France. Correspondence to Brigitte Sola, ICGM Inserm U363 Paris V. Bbt. G. Roussy, HBpital Cochin, 27 Rue du Fbg St Jacques, 75014, Paris, France. Received 11 May 1992; revised and accepted for publication 3 August 1992 0 1993 Academic Press Limited 1043-4666/93/010008+08 $08.00/O KEY WORDS: growth factor/hematopoiesis/PDGF receptor/ tyrosine kinase 8 and a cytoplasmic tyrosine kinase domain interrupted by a kinase insert (reviewed in ref. 4). Moreover, on mouse and human chromosomes, the CSF-1R gene is linked to the P-type platelet-derived growth factor (PDGF) receptor gene which also belongs to the same receptor subfamily. Both genes are localized on mouse chromosome 185,6 and on human chromosome 57,s in very close proximity since the polyadenylation signal of the PPDGFR gene is separated by only 500 bp from the most distal c-fms promoter.9 As viral enhancers do not exclusively act on the most adjacent promoter and because of the close proximity between the c-f& and the PPDGFR genes, we studied the PPDGFR gene expression in F-MuLV-induced myeloblastic leukemias. We found that 7 out of 21 cells lines tested expressed a normal sized and two others a truncated form of pPDGFR mRNA and that PDGFR gene expression was probably not related to proviral integration in the Fim-2 region. Since the PPDGFR expression was rather unexpected in immature hematopoietic cells, we also studied a series of 23 cell lines belonging to other hematopoietic lineages. /3PDGF receptors were also expressed in multipotential and in mast cell lines but not in erythroid, lymphoid or megakaryocytic cell lines. We also demonstrated that high affinity PPDGF receptors were expressed at the cell surface and that CYTOKINE, Vol. 5, No. 1 (January), 1993: pp 8-15